5beta - n - methylamino - ethoxyimino - 5h - dibenzo - (a,d) - 10,11 - dihydrocycloheptene and non-toxic pharmaceutically acceptable salts thereof and their production



United States Patent US. Cl. 260-566 1 Claim ABSTRACT OF THE DISCLOSURESfi-N-methylamino-ethoxyimino-SH-dibenzo [a,d]10,ll-dihydro-cycloheptene and pharmaceutically acceptable non-toxic saltsthereof possess antidepressive activity in humans and in vitro exhibitstrong spasmolytic effect.

The present invention relates to new basically substituted oximes ofSH-dibenzo [a,d]-10,1l-dihydro-cycloheptene-S-one, their non-toxicpharmaceutically acceptable salts and procedure for making same, the newcompounds possessing useful pharmacological and pharmacodynamicproperties when administered by the usual routes for these types ofcompounds.

Basically substituted SH-dibenzo [a,d]-l0,ll-dihydrocycloheptenes haveachieved importance as antidepressive agents [1. Med. Chem., 7 (1964)pages 390-392; J. Med. Chem., 7, 88-94 (1964); J. Med. Pharm. Chem.,4,411- 416 1961) Basically substituted oximes of S-H-dibenzo [a,d]-l0,11-dihydro-cycloheptene-S-one, however, have not heretofore beendisclosed or described in the literature. It has now been found that3-N-methy1amino-ethoxyimino-5H- dibenzo-[a,d]10,1l-dihydrocyclohepteneof the formula:

have valuable and useful pharmacological properties.

They are also active in various animal experiments which giveindications of the quality of their antidepressive (thymoleptic)activity in human beings.

The compound has moreover a strong spasmolytic elfect in vitro.

Non-toxic pharmaceutically acceptable acids which are suitable for saltformation are, e.g., acetic acid, propionic acid, lactic acid, maleicacid, fumaric acid, succinic acid, tartaric acid, citric acid, salicylicacid, naphthalene-1,5-

"ice

disulphonic acid, phosphoric acid, hydrochloric acid, and the like.

It has further been found that the new compounds can be produced byeither reacting a SH-dibenzo [a,d]-l0,lldihydro-cycloheptene of theformula:

with a hydroxylamine of the formula:

H NOCH CH NHCH or first converting with hydroxylamine into an oxime ofthe formula:

N-OH

and then allowing the same to react, in the form of a suitable metalsalt, with a halide of the formula:

HalogenCH -CH NHCH Example 1 1.3 g. of sodium are dissolved in 150 ml.of absolute ethanol. There are added thereto 11.2 g. of S-oximino-SH-dibenzo-[a,d]-10,ll-dihydro-cycloheptene. There 'is then introduced asolution of 6.5 g. of methyl-amino-ethylchloride in absolute ethanolwith stirring for one hour at room temperature. This is warmed overnightat C. and finally boiled for 1% hours under reflux. The product issuction filtered, the filtrate evaporated and the residue treated withcyclohexane. The cyclohexane extract is mixed with ethereal hydrochloricacid and the precipitated hydrochloride of5H-dibenzo-[a,d]-10,1l-dihydro-cycloheptene-S-(fl-methylamino-ethoxyamine)melts at 196 C. after decantating the solvent and recrystalizing fromacetone.

What is claimed is:

1. S-(B-N-methylamino ethoxyimino) 5H dibenzo- [a,d]-10,1l-dihydrocycloheptene or pharmaceutically acceptable non-toxic salts thereof.

References Cited UNITED STATES PATENTS 8/1966 Engelhard et al 260-S662/1966 Kollonitsch et a1. 260-570.8

US. Cl. X.R. 424-327

